Artículos (Medicina)

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  • Acceso AbiertoArtículo
    Prevention of type 2 diabetes in prediabetic patients by using functional olive oil enriched in oleanolic acid: The PREDIABOLE study, a randomized controlled trial
    (Wiley, 2019-07-31) Santos Lozano, José Manuel; Rada, Mirela; Lapetra, José; Guinda, Ángeles; Jiménez-Rodríguez, María C.; Cayuela, José A.; Ángel-Lugo, Antonio; Vilches Arenas, Ángel; Gómez Martín, Ana M.; Ortega Calvo, Manuel; Castellano, José M.; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III
    Aim: To assess whether the regular intake of an oleanolic acid (OA)-enriched olive oil is effective in the prevention of diabetes. Methods: In the PREDIABOLE study, prediabetic individuals (impaired fasting glucose and impaired glucose tolerance) of both sexes (176 patients, aged 30-80 years) were randomized to receive 55 mL/day of OA-enriched olive oil (equivalent dose 30 mg OA/day) [intervention group (IG)] or the same oil not enriched [control group (CG)]. The main outcome was the incidence of new-onset type 2 diabetes in both groups. Results: Forty-eight new diabetes cases occurred, 31 in the CG and 17 in the IG. The multivariate-adjusted hazard ratio was 0.45 (95% CI, 0.24-0.83) for the IG compared with the CG. Intervention-related adverse effects were not reported. Conclusions: The intake of OA-enriched olive oil reduces the risk of developing diabetes in prediabetic patients. The results of the PREDIABOLE study promote the use of OA in new functional foods and drugs for the prevention of diabetes in individuals at risk of developing it.
  • Acceso AbiertoArtículo
    Utility of pulmonary echography with a handheld ultrasound device in patients with acute coronary syndrome
    (Springer, 2023) Cristo Ropero, María José; Rivera Rabanal, Francisco Javier; Seoane García, Tania; Madrona Jiménez, Luis; Izquierdo Bajo, Álvaro; Hidalgo Urbano, Rafael; García Rubira, Juan Carlos; Vilches Arenas, Ángel; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. CTS-312: Análisis de la Demanda Sanitaria
    The objectives of this study are to establish the usefulness of lung ultrasound with a handheld device to predict the risk of developing heart failure with the need for mechanical ventilation (MV) in acute coronary syndrome (ACS). This is a prospective study of consecutive patients admitted because of ACS-type myocardial infarction, without data of HF at admission in a tertiary hospital, between February 2017 and February 2018. Lung ultrasounds were performed with a handheld cardiologic device in the first 24 h, and defined as echo-positive (PE+) when exams revealed 3 or more B-lines in 2 or more bilateral quadrants. We related this finding to the need for MV during admission. We included 119 patients (65.1 ± 12.8 year; 75.6% male, 24.4% female; 87.4% in Killip class I, 12.6% in Killip class II). Pulmonary echography was positive (PE+) in 21 patients (17.6%). The sensitivity of PE+ to predict MV was 93.3%, the specificity 93.3%, and the area under the curve 0.93. In Cox regression analysis adjusted by CRUSADE score and Killip class, PE+ patients had a hazard ratio of 64.55 (CI 7.87; 529.25, p < 0.001) of needing MV. PE+ was associated with more frequent use of inotropes and mortality. Pulmonary ultrasonography with a handheld echocardiograph was predictive of severe heart failure and the need for mechanical ventilation in ACS with high specificity and sensitivity.
  • Acceso AbiertoArtículo
    Long-Term Impact of an Educational Antimicrobial Stewardship Program on Hospital-Acquired Candidemia and Multidrug-Resistant Bloodstream Infections: A Quasi-Experimental Study of Interrupted Time-Series Analysis
    (2017-12-15) Molina, José; Peñalva, Germán; Gil Navarro, María Victoria; Praena, Julia; Lepe Jiménez, José Antonio; Olbrich, Peter; Jiménez-Mejías, Manuel Enrique; Garnacho Montero, José; Valencia, R.; Cordero Matia, María Elisa; Cisneros, José Miguel; García Cabrera, Emilio; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Microbiología; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Medicina; Junta de Andalucía
    Background The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. Methods We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). Results A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, −216.8 defined daily doses per 1000 OBDs; 95% confidence interval, −347.5 to −86.1), and was sustained during subsequent years (average reduction, −19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, −.003 to .039) reverted toward a decreasing trend of −0.130 per quarter (change in slope, −0.029; −.051 to −.008), and so did the mortality rate (change in slope, −0.015; −.021 to −.008). Conclusions This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.
  • Acceso AbiertoArtículo
    Outcomes of the PIRASOA programme, an antimicrobial stewardship programme implemented in hospitals of the Public Health System of Andalusia, Spain: an ecologic study of time-trend analysis
    (Elsevier Sci Ltd, 2020) Rodríguez-Baño, Jesús; Pérez-Moreno, M. A.; Peñalva, G.; Garnacho Montero, José; Pinto, C.; Salcedo, I.; Lupión Mendoza, Carmen; Pascual Hernández, Álvaro; Pascual Hernández, Álvaro; Pérez Lozano, María José; Valencia, R.; Cisneros, José Miguel; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Microbiología; Universidad de Sevilla. Departamento de Enfermería
    Objectives: Inappropriate antimicrobial use favours the spread of resistance, and multidrug-resistant microorganisms (MDR) are currently of major concern. Antimicrobial stewardship programmes (ASPs) are essential for improving antibiotic use in hospitals. However, their impact on entire healthcare sys tems has not been thoroughly assessed. Our objective was to provide the results of an institutionally supported ASP involving 31 public hospitals in Andalusia, Spain. Methods: We designed an ecologic time-series study from 1 January 2014 to 31 December 2017. Quar terly, data on indicators were collected prospectively, and feedback reports were provided. PIRASOA is an ongoing clinically based quality-improvement programme whose key intervention is the educational interview, regular peer-to-peer interventions between advisors and prescribers to reinforce the appro priate use of antibiotics. Seventy-two indicators were monitored to measure prescribing quality (inap propriate treatments), antimicrobial consumption (defined daily doses per 1000 occupied bed-days), incidence density of MDR per 1000 occupied bed-days and crude mortality rate associated with bloodstream infections. We used Joinpoint regression software to analyse the trends. Results: The quality of antimicrobial prescribing improved markedly, and the inappropriate treatment rate was significantly lower, with quarterly percentage change (QPC) ¼ 3.0%, p < 0.001. Total antimi crobial consumption decreased (QPC ¼ 0.9%, p < 0.001), specifically carbapenems, amoxicillin/clav ulanic acid, quinolones and antifungal agents, whereas antipseudomonal cephalosporin use increased. While the incidence of MDR showed a sustained decreasing trend (QPC ¼ 1.8%; p 0.002), the mortality of patients with bloodstream infections remained stable (QPC ¼ 0.2%, p 0.605). Conclusions: To date, the PIRASOA programme has succeeded in optimizing the use of antimicrobial agents and has had a positive ecologic result on bacterial resistance at level of an entire healthcare system.
  • Acceso AbiertoArtículo
    Has the COVID-19 pandemic wiped out the seasonality of outpatient antibiotic use and influenza activity? A time-series analysis from 2014 to 2021
    (Elsevier Sci Ltd, 2022-06) Guisado Gil, Ana Belén; Benavente, Regina Sandra; Villegas Portero, Román; Gil Navarro, María Victoria; Valencia, R.; Peñalva, Germán; Cisneros, José Miguel; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública; Universidad de Sevilla. Departamento de Medicina
    Objective: To assess the influence of the emergence of severe acute respiratory syndrome coronavirus 2 and the implementation of public health measures on the seasonality of outpatient antibiotic use and their possible association with the incidence of influenza. Methods: We performed a time-series ecological study in 1516 primary care centres of Andalusia, Spain, comparing the coronavirus disease 2019 period (April 2020 to March 2021) with the 6 previous years. We assessed the number of packs and defined daily doses per 1000 inhabitants of antibacterials and key antibiotics commonly used for acute respiratory tract infections and the number of influenza-positive cases per 100 000 inhabitants. We calculated the correlation between variables and analyzed the sea sonal patterns and differences in quarterly antibiotic use. Results: For all quarters, a significant correlation was observed between influenza activity and antibiotic use (Spearman's r ¼ 0.94; p < 0.001). Before the pandemic period, both variables presented similar seasonal patterns. After the start of the pandemic, influenza activity was suppressed and the pattern of antibiotic use flattened into a straight line (R2 ¼ 0.96; p ¼ 0.022) with a quarterly change of 3.9% (p ¼0.007). Total antibiotic use and antibiotics used for treating acute respiratory tract infections showed significant reductions in all quarters compared to the previous year (p < 0.01). Discussion: The coronavirus disease 2019 pandemic has strongly influenced the seasonality of antibiotic use in primary care. The decline in respiratory viruses, among which the influenza virus is a major player that may act as a proxy for general prevalence, is proposed as a reason for the flattening of the seasonal fluctuations of outpatient antibiotic use in our region. Ana Belen Guisado-Gil, Clin Microbiol Infect 2022;28:881.e7e881.e12
  • Acceso AbiertoArtículo
    A social media listening study of patients' experiences relating to metabolic dysfunction-associated steatotic liver disease: The LISTEN-MASLD study
    (Elsevier España, 2024) Lazarus, Jeffrey V.; Alazawi, William; Basuroy, Ron; Castera, Laurent; Estulin, Dmitry; Koulla, Yiannoula; Prasad, Preethy; Romero Gómez, Manuel; Takahashi, Hirokazu; Wong, Vincent Wai-Sun; Schattenberg, Jörn M; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. CTS532: Unidad de hepatología (Sistema Sanitario Público de Andalucía. Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI))
    Introduction and Objectives: Patients increasingly use social media to share and access health-related information and experiences. This study employed social media listening to gain patient-centric insights into metabolic dysfunc tion-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). Materials and Method: Publicly available social media data was collected between November 4th, 2020, and November 4th, 2022, about MASLD from eight countries: Brazil, China, France, Germany, Japan, South Korea, Spain, and the United Kingdom. The analysis involved capturing patient conversations on their journey stages (causes-risk factors, symptoms, diagnosis, and treatment), unmet needs, and impact on patient’s qual ity of life (QoL) from various social media platforms to gain insights associated with MASLD. Results: A total of 1600 patient-centric posts were analyzed. The patient journey was the most prevalent topic (92 %) mentioned, followed by comorbidities (38 %) and interactions with HCPs (26 %, health care professio nals). Key causes discussed included unhealthy diet (39 %) and overweight/obese (32 %), while the most men tioned symptoms were fatigue (20 %) and pain or abdominal discomfort (20 %). Ultrasound (n=170/553, 31 %) was the most used diagnosis, followed by blood tests (n=130/553, 24 %) and liver function tests (n=91/553, 16 %). Lifestyle management techniques were mainly the standard of care, followed by treatment (n=270/ 1061, 25 %) and follow-ups with HCPs (n=133/1061, 13 %). Over half (54 %) of the QoL discussion (n=104/192) focused on patients’ comorbidities, and 27 % on disease severity, indicating that having MASLD in moderate to severe form with comorbidities significantly affects patients’ quality of life. An emotional analysis revealed that patients were worried and frustrated about their condition but were also hopeful and determined to improve their health. Nearly 38 % of the posts mentioned that patients were emotionally affected by negative feelings, especially those with multiple comorbidities. Lack of access to knowledgeable HCPs and treatment options were the most frequently discussed unmet needs. Conclusions: This analysis of NAFLD patient experiences introduces a unique approach for deriving insights into patients’ experiences and their impact on QoL. These insights have the potential to complement conven tional methods and foster patient-centric research.
  • Acceso AbiertoArtículo
    Unveiling spatial clusters of systemic sclerosis mortality in Spain: A comprehensive geographical analysis
    (Elsevier, 2024-12-16) Cayuela, Lucía; Pereyra-Rodríguez, José-Juan; Collado Ramos, Paz; Garvín Grande, Nuria; Cayuela Domínguez, Aurelio; Universidad de Sevilla. Departamento de Medicina; Pereyra-Rodríguez, José-Juan
    Objectives: This study examined the spatial patterns of systemic sclerosis mortality in Spain from 2003 to 2022, identifying provincial-level clusters and sex-specific differences to explore potential underlying factors. Methods: Mortality and population data (2003-2022) were sourced from the National Institute of Statistics. Age-standardized mortality rates were calculated, and spatial patterns were analyzed using standardized mortality ratios and smoothed relative risks via the Besag, York, and Mollié model, with statistical inference performed using the Integrated Nested Laplace Approximation (INLA) technique. Spatial clustering was assessed using Tango’s and Kulldorff’s tests. Results: A total of 2,016 SSc deaths were recorded, revealing a marked gender disparity. SSc mortality rates showed a consistent annual increase of 2.1% for both sexes, with women experiencing rates approximately 3.4 times higher than men. Age-specific analysis demonstrated higher mortality rates among women across all age groups, with an average sex ratio of 2.9, and rates increased with age for both sexes. Spatial analysis identified significant clusters of elevated SSc mortality in northwestern Spain, primarily in León and Asturias, with additional clusters extending to nearby provinces. These regions, characterized by silica mining and related industries, exhibited notable variations between men and women in the specific provinces affected. Conclusions: This study identifies significant geographic and sex-based disparities in SSc mortality across Spain, with prominent clusters in the north. The results highlight the potential impact of environmental and occupational exposures on disease outcomes, emphasizing the need for targeted public health interventions in high-risk areas.
  • Acceso AbiertoArtículo
    COVID-19 clinical phenotypes in vaccinated and nonvaccinated solid organ transplant recipients: a multicenter validation study
    (Nature Publishing Group, 2024-12-03) Infante-Domínguez, Carmen; Salto Alejandre, Sonsoles; Álvarez Marín, Rocío; Sabé, Nuria; Ramos-Martínez, Antonio; Moreno, Asunción; Sanchez Cespedes, Javier; Gutiérrez Gutiérrez, Belén; Rodríguez-Baño, Jesús; Pachón Díaz, Jerónimo; Cordero Matia, María Elisa; Cisneros, José Miguel; Universidad de Sevilla. Departamento de Medicina; Gobierno de España; Instituto de Salud Carlos III
    Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51–69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO2 < 95% at admission. All-cause mortality occurred in 105 (21.5%) cases. It was higher in nonvaccinated versus vaccinated SOTR (23.4% vs 13.8%, P = 0.04). Patients in the entire cohort were classified into phenotypes A (n = 149, 30.5%), B (n = 187, 38.3%), and C (n = 152, 31.1%), with mortality rates of 8.7%, 16.6%, and 40.1%, respectively, which were similar to those of nonvaccinated SOTR (9.5%, 16.7%, and 52.0%) and lower in vaccinated SOTR (4.4%, 15.8%, and 17.3%, respectively), with difference between nonvaccinated and vaccinated in the phenotype C (P < 0.001). In conclusion, COVID-19 clinical phenotypes are useful in SOTR, and all-cause mortality decreases in vaccinated patients.
  • EmbargoArtículo
    Cortical hypometabolism in Parkinson’s disease is linked to cholinergic basal forebrain atrophy
    (Springer, 2024) Labrador-Espinosa, Miguel Á.; Silva-Rodríguez, Jesús; Okkels, Niels; Muñoz-Delgado, Laura; Horsager, Jacob; Castro-Labrador, Sandra; Franco-Rosado, Pablo; Castellano-Guerrero, Ana María; Iglesias Camacho, Elena; San-Eufrasio, Manuela; Macías-García, Daniel; Jesús, Silvia; Adarmes-Gómez, Astrid; Ojeda-Lepe, Elena; Carrillo, Fátima; Martín Rodríguez, Juan Francisco; Roldán Lora, Florinda; García Solís, David; Borghammer, Per; Mir Rivera, Pablo; Grothe, Michel J.; Universidad de Sevilla. Departamento de Psicología Experimental; Universidad de Sevilla. Departamento de Medicina; Ministerio de Ciencia e Innovación (MICIN). España; Instituto de Salud Carlos III; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Fundación Alicia Koplowitz
    Cortical hypometabolism on FDG-PET is a well-established neuroimaging biomarker of cognitive impairment in Parkinson’s disease (PD), but its pathophysiologic origins are incompletely understood. Cholinergic basal forebrain (cBF) degeneration is a prominent pathological feature of PD-related cognitive impairment and may contribute to cortical hypometabolism through cholinergic denervation of cortical projection areas. Here, we investigated in-vivo associations between subregional cBF volumes on 3T-MRI, cortical hypometabolism on [18F]FDG-PET, and cognitive deficits in a cohort of 95 PD participants with varying degrees of cognitive impairment. We further assessed the spatial correspondence of the cortical pattern of cBF-associated hypometabolism with the pattern of cholinergic denervation in PD as assessed by [18F]FEOBV-PET imaging of presynaptic cholinergic terminal density in a second cohort. Lower volume of the cortically-projecting posterior cBF, but not of the anterior cBF, was significantly associated with extensive neocortical hypometabolism [p(FDR) < 0.05], which mediated the association between cBF atrophy and cognitive impairment (mediated proportion: 43%, p < 0.001). In combined models, posterior cBF atrophy explained more variance in cortical hypometabolism (R2 = 0.26, p < 0.001) than local atrophy in the cortical areas themselves (R2 = 0.16, p = 0.01). Topographic correspondence analysis with the [18F]FEOBV-PET pattern revealed that cortical areas showing most pronounced cBF-associated hypometabolism correspond to those showing most severe cholinergic denervation in PD (Spearman’s ρ = 0.57, p < 0.001). In conclusion, posterior cBF atrophy in PD is selectively associated with hypometabolism in denervated cortical target areas, which mediates the effect of cBF atrophy on cognitive impairment. These data provide first-time in-vivo evidence that cholinergic degeneration represents a principle pathological correlate of cortical hypometabolism underlying cognitive impairment in PD.
  • Acceso AbiertoArtículo
    La hiponatremia: un desafío clínico y terapéutico. Cuando no parece lo que es
    (Sociedad Española de medicina interna, 2024-11-30) Luque-Linero, Paula; Sánchez-Sánchez, Jaime; Carmona Nimo, Eduardo; Universidad de Sevilla. Departamento de Medicina
    El síndrome de secreción inadecuada de hormona antidiurética (SIADH) es un diagnóstico de exclusión en pacientes que sufren de hiponatremia. La etiología puede ser diversa, siendo la tuberculosis pulmonar una causa descrita pero poco frecuente. La urea se propone como un fármaco eficaz en el tratamiento de la hiponatremia por SIADH. A continuación, presentamos el caso de un paciente con SIADH secundario a una tuberculosis pulmonar, cuya hiponatremia mejoró tras el comienzo de urea.
  • Acceso AbiertoArtículo
    Increasing prevalence of psoriasis in Spain: A population-based study (2018-2022)
    (2024-11-18) Cayuela, Lucía; Pereyra-Rodríguez, José-Juan; Hernández Rodríguez, Juan Carlos; Rodríguez Fernández-Freire, Lourdes; Cayuela, Aurelio; Universidad de Sevilla. CTS1088: Enfermedades Inmunomediadas
    Objectives: This study aimed to investigate the prevalence of psoriasis in Spain from 2018 to 2022 and analyze trends by sex and age groups. Methods: We used the Primary Care Clinical Database (BDCAP) to identify individuals coded with psoriasis (S91) during the study period. Population data for calculating rates was obtained from the Primary Care Information System (SIAP). Crude, age- and sex-specific, and standardized prevalence rates were calculated. Joinpoint analysis assessed annual percentage change (APC) in prevalence. Results: The estimated psoriasis prevalence in Spain in 2022 was 1.9%. Psoriasis prevalence increased substantially by 43.3% (from 692,317 to 991,832 cases) over the study period. We observed a clear increase in both crude and standardized prevalence rates for men (7.2% annual increase) and women (8.3% annual increase) throughout the study period. Men consistently had slightly higher prevalence rates than women. Prevalence increased with age, reaching a peak in the 70-74 age group for men and 60-64 for women, before declining in older age groups. Conclusions: This study revealed a concerning increase in psoriasis prevalence in Spain, independent of population aging. Increased disease awareness, improved diagnostics, and greater treatment seeking behavior are potential explanations. Further research is needed to explore the underlying causes of this rise and inform public health interventions.
  • Acceso AbiertoArtículo
    The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease
    (Elsevier, 2024-07) Younossi, Zobair M.; AlQahtani, Saleh A.; Funuyet Salas, Jesús; Romero Gómez, Manuel; Yilmaz, Yusuf; Keklikkiran, Caglayan; Lazarus, Jeffrey V.; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla: CTS: Unidad de Hepatología (Sistema Sanitario Público de Andalucía. Fundación Pública Andaluza para la Gestión de la Investigación en Salud de Sevilla (FISEVI))
    Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and po tential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a surveyabout disease burden in NAFLD. Participants completed a 35 item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe,16% USA,18% Asia) and 778 competed CLDQ-NASH. Of the studygroup, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest inde pendent predictor of lower HRQL scores (beta from-5% to-8% of score range size, p<0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncom fortable with the term “fatty liver disease” with lower Emotional Health scores (all p<0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients’ self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers’ perception may not adequately reflect patients’ perspective and experience with the disease.
  • Acceso AbiertoArtículo
    Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study
    (Elsevier, 2024-04) Maldonado, Natalia; López Hernández, Inmaculada; García Montaner, Andrea; López-Cortes, Luis Eduardo; Martínez Pérez-Crespo, Pedro María; Retamar Gentil, Pilar; Rodríguez-Baño, Jesús; Pascual Hernández, Álvaro; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Microbiología
    Background Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. Methods Ecolibloodisolatesfromamulticentrecross-sectionalstudyofpatientsolderthan14yearspresentingwithsepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shock criteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A, B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ2 or Fisher’s exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. Findings We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0⋅0045). Median virulence score was higher in group 1 (median 25⋅0 [IQR 20⋅5–29⋅0) than in group 2 (median 14⋅5[9⋅0–20⋅0]; p<0⋅0001) and group 3 (median 21 [16⋅5–23⋅0]; p<0⋅0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29–35]) than the other predominant clones (median range 21–28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. Interpretation In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection.
  • Acceso AbiertoArtículo
    Current practice of screening and antimicrobial prophylaxis to prevent Gram-negative bacterial infection in high-risk haematology patients: results from a pan-European survey
    (Sage Publications Ltd, 2024-10-29) Stemler, Jannik; Gavriilaki, Eleni; Hlukhareva, Oksana; Khanna, Nina; Neofytos, Dionysios; Akova, Murat; Pagano, Livio; Cisneros, José Miguel; Cornely, Oliver A.; Salmanton-Garcia, Jon; Universidad de Sevilla. Departamento de Medicina
    Background: Bacterial infections frequently occur in haematological patients, especially during prolonged neutropenia after intensive chemotherapy, often leading to bloodstream infections and pneumonia. Objective: Routine antimicrobial prophylaxis (AMP) for high-risk haematology patients is still debated while prevalence of multi-drug resistant (MDR) Gram-negative bacteria (GNB) is rising globally. We aimed to assess the current practice of AMP in this population. Design: Cross-sectional observational survey study. Methods: Haematologists and infectious diseases physicians Europewide were invited to an online survey including questions on routine screening for GNB, incidence of MDR-GNB colonization, antimicrobial prophylaxis practices, rates of bloodstream infections (BSI), ICU admission and mortality differentiated by infections due to GNB versus MDR-GNB. Results: 120 haematology centres from 28 countries participated. Screening for MDR-GNB is performed in 86.7% of centres, mostly via rectal swabs (58.3%). In 39.2% of routine AMP is used, mostly with fluoroquinolones. Estimates of GNB-BSI yielded higher rates in patients not receiving anti-GNB prophylaxis than in those who do for E. coli (10% vs 7%) Klebsiella spp. (10% vs 5%), and Pseudomonas spp. (5% vs 4%). Rates for MDR-GNB infection were estimated lower in centres that administer AMP for MDR E. coli (5% vs 3%) Klebsiella spp. (5% vs 3%), and Pseudomonas spp. (2% vs 1%). In an exploratory analysis, Southern and Eastern European countries expected higher rates of MDR-GNB infections with lower ICU admission and mortality rates which may be subject to estimation bias. Conclusion: Screening for MDR-GNB is frequently performed. AMP against GNB infections is still often implemented. Estimated BSI rates are rather low, while the rate of MDR-GNB infections rises. Tailored prophylaxis including antimicrobial stewardship becomes more important.
  • Acceso AbiertoArtículo
    A phase III randomized controlled trial of plitidepsin, a marine-derived compound, in hospitalized adults with moderate covid-19
    (Oxford University Press, 2024-08-26) Landete, Pedro; Caliman-Sturdza, Olga Adriana; Lopez-Martin, Jose A.; Preotescu, Liliana; Luca, Mihaela-Catalina; Kotanidou, Anastasua; Cisneros, José Miguel; Varona, Jose Felipe; Universidad de Sevilla. Departamento de Medicina
    Background. Plitidepsin has shown potent preclinical activity against severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (COVID-19). NEPTUNO, a phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. Methods. Included patients had documented severe acute respiratory syndrome coronavirus 2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. Results. After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19–related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio, 1.37; 95% confidence interval, .96–1.96; P = .08 for plitidepsin 1.5 mg vs control; hazard ratio, 1.06; 95% confidence interval, .73–1.53; P = .78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. Conclusions. Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. Results from this phase III trial suggest that plitidepsin, a first-in-class antiviral, may have a positive benefit-risk ratio in the management of hospitalized patients requiring oxygen therapy for moderate COVID-19.
  • Acceso AbiertoArtículo
    Could the Adoptive Transfer of Memory Lymphocytes be an Alternative Treatment for Acinetobacter baumannii Infections?
    (MDPI, 2024-09-30) Cebrero-Cangueiro, Tania; Herrera-Espejo, Soraya; Paniagua, María; Labrador-Herrera, Gema; Cisneros, José Miguel; Universidad de Sevilla. Departamento de Medicina; Consejeria de Salud de la Junta de Andalucia; European Development Regional Fund "A way to achieve Europe"; Instituto de Salud Carlos III; Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases
    We evaluated the efficacy of the adoptive transfer of memory B, CD4+, and CD8+ T lymphocytes compared with sulbactam and tigecycline in an experimental murine pneumonia model by two multidrug-resistant Acinetobacter baumannii strains, colistin-susceptible AbCS01 and colistin-resistant AbCR17. Pharmacodynamically optimized antimicrobial dosages were administered for 72 h, and intravenous administration of 2 × 106 of each of the memory cells in a single dose 30 min post-infection. Bacterial lung and blood counts and mortality rates were analyzed. Results showed that a single dose of memory B or CD4+ T cells was as effective as sulbactam in terms of bacterial clearance from the lungs and blood compared with the untreated mice or the tigecycline-treated mice inoculated with the AbCS01 strain. In the pneumonia model by AbCR17, a single dose of memory B or CD4+ T cells also reduced the bacterial load in the lungs compared with both antibiotic groups and was more efficacious than tigecycline in terms of blood clearance. Regarding survival, the adoptive transfer of memory B or CD4+ T cells was as effective as three days of sulbactam treatment for both strains. These data suggest that adoptive memory cell transfer could be a new effective treatment of multidrug-resistant A. baumannii infections.
  • Acceso AbiertoArtículo
    Effects of age, period, and cohort on the incidence of psoriasis in Spain: a 30-year review (1990-2019)
    (Elsevier, 2024) Cayuela, Lucía; Pereyra-Rodríguez, José-Juan; Hernández-Rodríguez, Juan Carlos; Rodríguez Fernandez-Freire, L.; Cayuela, Aurelio; Universidad de Sevilla. Departamento de Medicina
    Aim This study aimed to investigate the effects of age, period, and cohort on the incidence of psoriasis in Spain from 1990 through 2019 using the Global Burden of Disease (GBD) database and age-period-cohort (A-P-C) analysis. Methods We conducted an ecological trend study to analyze the incidence rates of psoriasis in Spain from 1990 through 2019. Joinpoint Regression Program, Version 5.0.2 - May 2023; Surveillance Research Program, National Cancer Institute and National Cancer Institute A-P-C tools were used to identify trends and assess the effects of age, period, and cohort. Results From 1990 through 2019, an estimated 2.99 million cases of psoriasis were diagnosed in Spain, with a mean annual increase of 0.49%. Significant decreases in age-standardized incidence rates (ASIR) were reported for both sexes, with women consistently maintaining a slightly higher ASIR. Joinpoint analysis revealed multiple turning points in the downward trend, indicating periods of stabilization. A-P-C analysis demonstrated significant declines in both net (overall trend) and local drift (age-specific trends), indicating a broad decrease in the incidence of psoriasis across most age groups. While the risk of psoriasis increased with age, peaking in the 50–54 age group, it declined thereafter. Furthermore, the analysis revealed a continuous decline in risk from 1990 through 2019 for both sexes, with individuals born in the early 21st century exhibiting a significantly lower risk vs those born in the early 20th century. Conclusion This study observed a slight decline in the reported psoriasis ASIR in Spain, potentially due to reduced exposure to risk factors. However, limitations in data and the complexity of factors influencing the incidence of psoriasis require further research.
  • Acceso AbiertoArtículo
    Mitomycin C as an anti-persister strategy against klebsiella pneumoniae: toxicity and synergy studies
    (MDPI, 2024-08-28) Pacios, Olga; Herrera-Espejo, Soraya; Armán, Lucía; Ibarguren-Quiles, Clara; Blasco, Lucía; Bleriot, Inés; Cisneros, José Miguel; Pachón-Ibáñez, María Eugenia; Tomás, María; Universidad de Sevilla. Departamento de Medicina
    The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked using both cytotoxicity assays and flow cytometry.
  • Acceso AbiertoArtículo
    Patch test results to the Spanish baseline patch test series according to age groups: a multicentric prospective study from 2019 to 2023
    (Wiley, 2024-09-12) Pesqué, David; Planella‐Fontanillas, Nidia; Borrego, Leopoldo; Sanz‐Sánchez, Tatiana; Zaragoza‐Ninet, Violeta; Serra‐Baldrich, Esther; Pereyra-Rodríguez, José-Juan; Giménez‐Arnau, Ana María; Universidad de Sevilla. Departamento de Medicina
    Introduction Patch test results may be influenced by age-related factors. However, there is still discordant evidence between age and patch test results. Objectives We aim to evaluate the patch test results reflecting skin sensitisation, their relevance and association with clinical features by age group. Methods Prospective multicentric study of all patients patch tested with the Spanish baseline series in participating centres. Age groups were pre-defined as children (0- to 11-years), adolescents (12- to 18-years), young adults (19- to 30-years), middle-aged adults (31- to 65-years) and older adults (≥66-years). Occurrence of sensitisation, relevance and clinical features were compared by age group. Factors associated with skin sensitisation were investigated with multivariate logistic regression. Results A total of 13 368 patients were patch-tested. Differences in positive patch test results and relevance by age were detected with the highest proportion in middle-aged adults. Age-related trend differences were found for nickel, potassium dichromate, caines, colophony, Myroxylon pereirae resin, 2-hydroxyethyl methacrylate and limonene hydroperoxide. The multivariate logistic analysis (adjusted for sex, atopic dermatitis, body location and occupational dermatitis) showed an association between the age group of 31–65 (OR: 1.41, 95% CI: 1.26–1.58) and above 66-years (OR: 1.15, 95% CI: 1.01–1.32) with a higher proportion of positive results, compared with young adults. Conclusions Positive patch test results vary according to age, with the highest occurrence in middle-aged adults. Most haptens did not present age-related differences, reinforcing the use of baseline series regardless of age.
  • EmbargoArtículo
    Patterns and trends in melanoma mortality in Spain (1999–2022)
    (Springer, 2024-10-05) Cayuela, Lucía; Hernández-Rodríguez, Juan Carlos; Pereyra-Rodríguez, José-Juan; Sendín-Martín, Mercedes; Cayuela, Aurelio; Universidad de Sevilla. Departamento de Medicina
    Aim To examine melanoma mortality trends in Spanish Autonomous Communities from 1999 to 2022, focusing on gender and age differences. Methods Data from the National Statistics Institute were used to calculate age-standardized mortality rates (ASMRs). Joinpoint regression identified trend changes. Results Melanoma mortality varied significantly by region, gender, and age. Eastern Spain had higher male mortality, while western regions had lower rates. Asturias had higher female mortality, with lower rates in Andalusia, Extremadura, and Castilla-La Mancha. Men generally exhibited higher ASMRs than women, with variations across regions. While ASMRs remained stable in most areas, Madrid experienced a notable decline (AAPC: − 1.3%). A national trend reversal occurred in 2014 (AAPC: − 1.3%). For individuals aged 45–74 years, Catalonia saw a significant decrease (AAPC: − 1.1%, p < 0.05), whereas Andalusia experienced an increase (APC: 2.1% since 2007). Nationally, ASMRs for this age group declined (AAPC: − 0.7%). Among those aged 75 years and over, ASMRs varied considerably, with increases observed in Andalusia and Aragon. Nationally, male ASMRs rose (AAPC: 1.6% per year), while female rates were stable. Regional disparities were evident, with higher female mortality in the Balearic Islands and fluctuating rates in the Community of Madrid (an increase followed by a decrease after 2015). The gender gap in mortality varied across regions, with some areas showing a narrowing gap and others widening disparities. Conclusion Continuous monitoring of melanoma mortality, especially among men and older adults, is crucial. Public health efforts should address regional disparities, improve early detection, and enhance treatment access to optimize outcomes nationwide.